Apoptosis and oxidative stress are mechanisms associated with osteoporosis. We previously reported that cadmium induces these mechanisms in an osteoblast cell line. This study aims to determine signaling pathways involved in cadmium induced apoptosis in tumor derived Saos-2 and non-tumor derived MC3T3-E1 osteoblasts. We hypothesize that ERK is up-regulated in the presence of CdCl2, and predict that an ERK inhibitor will prevent cadmium-induced apoptosis. ERK activation was assessed by western blot after exposure to10 μM CdCl2. ERK was activated after 3 hours of CdCl2 exposure compared to controls in Saos-2 cells. We observed cadmium induced sustained ERK activation at later time points in both cell lines. These results indicate that acute and sustained ERK activation are involved in cadmium toxicity. Ongoing studies aim to link ERK activation to cadmium-induced apoptosis and altered osteoblast gene expression. Elucidation of cellular pathways involved in cadmium-induced osteotoxicity will lead to the understanding of underlying mechanisms of bone disease. Funded by INBRE P20RR016454 and NIH R15ES015866 grants.

Cadmium Exposure Leads to ERK Activation in Bone Forming Osteoblasts